Until now, no one has controlled the motion of fluids as disclosed herein. Devices are used that emit radiofrequency/microwave energy. The energy is directed to a target object, for example, a microchip that contains one or more material(s) that absorb(s) microwave energy. The microwave-generated heat energy causes physical changes in fluid-containing compartments, which in turn causes fluid movement.
Microfluidics
Microfluidics deals with the movement of small amounts of fluid (Burtsoff, 2004; Fitzgerald, 2002; Lesney, 2002; Roper et al., 2003; Hansen & Quake, 2003; Beebe et al., 2002; McDonald et al, 2000). Microfluidics is key toward the development of micro-synthesis, micro-separations, and lab-on-a-chip (or BioMEMS, biological MicroElectroMechanical Systems) technologies. Microfluidics assists in sample-preparation, rinsing, mixing, reaction, and other fluid handling needs for small volumes that cannot be performed in traditional ways. It is expected that microfluidics will revolutionize many applications including; proteomics and genomics research, high throughput and small sample analysis, on-site field and environmental analysis, clinical diagnostics, small-quantity chemical reactions, and combinatorial chemistry synthesis (McDonald et al., 2000). Additional benefits of microfluidics include automation, reduced waste, improved precision and accuracy, and disposability.
Microfluidics is a multi-faceted technology. Sub-technologies include electrophoresis, electrodynamics, semiconductor fabrication methods, fluid-moving technologies, labeling technology, laser fluorescence, and inkjet printing. This invention is concerned with the movement and mixing of fluids on a microfluidics platform, such as a chip.
Numerous approaches to moving fluids on microfluidics devices have been proposed and developed. These include; centrifugal force (Burtsoff, 2004), electrophoresis (Roper et al., 2003), electrokinetic pumping (Becker & Gartner, 2000), microsolenoid-triggered syringe pumps, piezoelectric pumps, gas bubble production (Lesney, 2002), hydrodynamic focusing, and passive fluid control (hydrophilic/hydrophobic repulsion) (Fitzgerald, 2002). Prior to this disclosure, microwave energy has not been used to move fluids.
Smart Materials
So-called smart materials are materials that can sense and dramatically respond to an environmental stimulus. Physical changes in smart materials include, but are not limited to; growth or shrinkage, precipitation, solubilization, and color change. Some examples are shown in Table 1 (Roy & Gupta, 2003, Morrison & Mosier, 2000, Fong, et al. 2002; Jeong & Gutowska, 2002).
TABLE 1Examples of Smart MaterialsStimulusResponsive MaterialspHDendrimers, poly(L-lysine)ester, poly(hydroxyproline),polysilamine, Eudragit S-100,chitosan, PMAA-PEG copolymerCa2+alginateMg2+chitosanorganic solventEudragit S-100temperaturePNIPAAm, poloaxymers, chitosan-glycerol phosphate-water,prolastin, polymer/proteinhybrid hydrogelsmagnetic fieldPNIPAAm hydrogels containingferromagnetic materialredox reactionPNIPAAm hydrogels containingtris (2,2′-bipyridyl) rutheniumIIelectric potentialpolythiophen gelIR radiationPoly(N-vinyl carbazole)compositeUV radiationPolyacrylamide crosslinked with4-(methacryloylamino) azobenzeneultrasoundDodecyl isocyanate-modified PEG-grafted poly(HEMA)microwave radiationorganic/aqueous liquid phasemixing
Smart materials can be used in bioseparation (Fong et al., 2002; Hoffman, 2000), drug delivery (Morrison & Mosier, 2000), tissue engineering, and gene delivery in gene therapy. They can also be used as molecular gates and switches, to aid in protein folding, and in flow control in microfluidics (Roy & Gupta, 2003).
Microwave Heating
Microwaves (including radiofrequency or RF electromagnetic radiation) are commonly used in wireless communication devices. Advances in microwave transmission have improved along with tremendous recent technological improvements in the satellite and communications industry (for example, in cell phones and wireless internet).
Microwaves are also well known in common kitchen appliances. Microwave ovens heat water-containing food rapidly because water is efficient at converting microwave energy to thermal energy. Kitchen microwave ovens emit microwaves at a frequency of 2.45 GHz, which is within the microwave absorption spectrum of water. Frequencies outside of the absorption spectrum of water would not heat food as well.
Another use for microwave heating is in chemical reaction applications (Bose et al., 1997; Bradley, 2001; Wathey et al., 2002; Lew et al., 2002). Microwave chemistry refers to the use of microwaves to accelerate chemical reactions (Mingos & Baghurst, 1991; Zlotorzynski, 1995). Microwave ovens specifically designed for use in carrying out microwave chemistry of bulk reaction solutions are commercially available (CEM Corporation (Matthews, N.C.), Milestone, Inc. (Monroe, Conn.), Biotage AB (Uppsala, Sweden), and PerkinElmer Instruments (Shelton, Conn.).
In yet other cases, microwave heating has been used in biochemistry applications. Microwave heating has been used to assist in protein staining (Nesatyy et al., 2002; Jain, 2002). Bulk microwave heating of samples has been used to accelerate antibody-antigen binding reactions in immunoassays, immunohistochemical assays, and DNA in-situ hybridization assays (Leong & Milios, 1986; Hjerpek et al., 1988; van den Kant et al., 1988; Boon & Kok, 1989; Kok & Boon, 1990; van den Brink et al., 1990; Slap 2003). In another case, microwaves were used as a heat source during PCR (Fermer et al., 2003).
The present invention is unique in that it discloses a novel means of using microwave energy to move and mix liquids without necessarily heating the liquids that are to be moved (isothermal fluid movement). Microwaves cause physical changes in materials that transform to induce fluidic effects.
Directed Microwave Heating
Dielectric materials are good at absorbing microwaves. Dielectrics have unique spectral characteristics of frequency versus heating ability, with different substances heating more effectively at different frequencies (Gabriel et al., 1998). Although dielectric heating is referred to here as microwave heating, dielectric heating can also occur at radio frequencies. This invention is intended to include those effects.
Dielectric heating depends on a number of factors including the frequency of the microwave irradiation and the absorption properties of the dielectric at that frequency. All dielectric materials have characteristic absorption spectra (frequency vs. heating ability). For example, in a conventional kitchen microwave oven, the microwave frequency (2.45 GHz) is very good for heating water, but not good for heating other materials (for example, a cup that holds the water). If the frequency of the microwave emission would be changed, in theory one could heat the cup but not the water (depending on the relative dielectric absorption characteristics of water and the cup).
In this invention, microwaves heat materials that are especially good at absorbing microwaves. The microwave-active materials are in thermal proximity to heat-susceptible materials. When the microwave-susceptible material is irradiated with microwaves, the heat susceptible material physically changes, causing fluid movement. The heat-susceptible materials need not be, by themselves, microwave-susceptible. Preferably, they will not be significantly microwave-susceptible. Most preferably, they will not be microwave-susceptible.
The invention has several advantages over alternative heating methods. These alternative methods include IR heating (for example, using a lamp, hair drier, or heat gun) and resistive heating. Resistive heating requires direct contact of the reaction surface with an electrical circuit and resistor, while the present invention obviates the need for direct contact. IR heating, although non-contact, is less efficient in rapidly heating a surface than is microwave heating. Finally, it is difficult to target infrared radiation, such as from a heat gun, especially in a millimeter or centimeter resolution pattern.